In our future research we aim to explore the relationship between the convulsant properties of methionine sulfoximine and its effect on cellular methylations. In particular we wish to follow up the observation that a single dose of MSO to rats causes marked reductions of S-adenosyl methionine (SAM) levels in the cerebral cortex, the cerebellum and the striatum, moderate reductions in the hippocampus, the midbrain and the hypothalamus and no reduction in the brainstem. Experimentally, we propose to test 4 alternative hypotheses of MSO action. 1) MSO increases the utilization of SAM, by eliciting higher than normal rates of methylation of the biogenic amines, norepinephrine, dopamine and tryptamine as well as of histamine and of ribosomal and transfer RNA. Concomitantly, there is little or no change in the concentration of cerebral S-adenosyl homocysteine (SAH). 2) SAM synthesis is affected by MSO. This should produce an involvement of the SAM synthesizing enzyme and changes in the turnover of SAM. 3) MSO interferes with the normal breakdown of SAH which accumulates; this, in turn, leads to a variable degree of inhibition of key methylation reactions and may culminate in the regional formation of abnormal excitatory metabolites. 4) MSO activates the hydrolysis of SAH. This results in excessive formation of metabolites of homocysteine, among them homocystic acid, a powerful neuronal excitant molecule. The present study is thus designed to delineate the mechanisc of operation of the regulatory system governing the cellular SAM/SAH ratio and hence the methylation index of the nerve cell under normal conditions and during the preconvulsant state.